Age related macular degeneration (AMD) is one of the primary causes of blindness in the U.S. A wealth of powerful new treatments, especially anti-VEGF agents, has recently become available to restore visual function in choroidal neovascularization (CNV), the most severe form of AMD. The risk of ocular adverse events increases with repeated intravitreal treatment injections. Ideally a patient-specific dosing strategy with the minimally necessary number of anti-VEGF injections would be employed. This study will address which patient-specific properties of the intra- and sub-retinal fluid, cysts, and retinal layers of the macula (obtained from 3D spectral domain optical coherence tomography or OCT) (i) are associated with individual response to anti-VGEF treatment, and (ii) can predict proper treatment timing and response. The main hypothesis motivating the proposed research is that a model of retinal response to initial anti-VEGF treatment for CNV, based on quantitative 3D OCT-derived measures, can predict the timing of retreatment.We have identified the following specific aims: Aim 1: Further refine and validate a comprehensive set of analysis methods and approaches for 3D spectral OCT image analysis in the presence of wet AMD pathology (Symptomatic Exudate Associated Derangements or SEADs) and assess its performance by comparison to expert analyses. Aim 2: Determine associations between standard 2D Spectralis OCT clinical readings from retinal specialists and quantitative SEAD- and layer-derived measures from 3D Cirrus OCT. Aim 3: Determine how well the quantitative SEAD- and layer-derived measures from 3D OCT predict the patient-specific outcome parameters in response to post-induction anti-VEGF treatment in patients with CNV, in order to predict the timing of retreatment. The work will be performed prospectively in in-vivo spectral-domain OCT images acquired during the course of CNV disease treatment. We will repeatedly image 200 patients with choroidal neovascularization before and during treatment and during the 1-year follow-up phase. PUBLIC HEALTH RELEVANCE: Three dimensional spectral OCT imaging provides a wealth of information about the morphology and tissue characteristics of human retinal. We propose to study structural and functional relationships of the macular intraretinal layers using this new 3-D OCT imaging device and relate the information about patient-specific retinal composition and structure with treatment outcome in age-related macular degeneration. This study has potentially important consequences for image guided treatment of this blindness-causing disease.